Chemopreventive Activity of MGN-3/Biobran Against Chemical Induction of Glandular Stomach Carcinogenesis in Rats and Its Apoptotic Effect in Gastric Cancer Cells

In the current study, we investigated the chemopreventive activity of arabinoxylan rice bran, MGN-3/Biobran, against chemical induction of glandular stomach carcinogenesis in rats. Gastric cancer was induced by carcinogen methylnitronitrosoguanidine (MNNG), and rats received MNNG alone or MNNG plus Biobran (40 mg/kg body weight) for a total of 8 months. Averaged results from 2 separate readings showed that exposure to MNNG plus Biobran caused gastric dysplasia and cancer (adenocarcinoma) in 4.5/12 rats (9/24 readings, 37.5%), with 3.5/12 rats (7/24 readings, 29.2%) showing dysplasia and 1/12 rats (8.3%) developing adenocarcinoma. In contrast, in rats treated with MNNG alone, 8/10 (80%) developed dysplasia and adenocarcinoma, with 6/10 rats (60%) showing dysplasia and 2/10 rats (20%) developing adenocarcinoma. The effect of combining both agents was also associated with significant suppression of the expression of the tumor marker Ki-67 and remarkable induction in the apoptotic gastric cancer cells via mitochondrial-dependent pathway as indicated by the upregulation in p53 expression, Bax expression, downregulation in Bcl-2 expression, an increase in Bax/Bcl-2 ratio, and an activation of caspase-3. In addition, Biobran treatment induced cell-cycle arrest in the subG1 phase, where the hypodiploid cell population was markedly increased. Moreover, Biobran treatment protected rats against MNNG-induced significant decrease in lymphocyte levels. We conclude that Biobran provides protection against chemical induction of glandular stomach carcinogenesis in rats and may be useful for the treatment of human patients with gastric cancer.

Download Full-text

Chrysin Alters microRNAs Expression Levels in Gastric Cancer Cells: Possible Molecular Mechanism

Drug Research ◽

10.1055/s-0042-119647 ◽

2017 ◽

Vol 67 (09) ◽

pp. 509-514 ◽

Cited By ~ 13

Author(s):

Farideh Mohammadian ◽

Younes Pilehvar-Soltanahmadi ◽

Shahriar Alipour ◽

Mehdi Dadashpour ◽

Nosratollah Zarghami

Keyword(s):

Gastric Cancer ◽

Gastric Carcinoma ◽

Cancer Cells ◽

Molecular Mechanism ◽

Molecular Mechanisms ◽

Gastric Cancer Cells ◽

Gastric Carcinoma Cell ◽

Expression Levels ◽

Mirnas Expression ◽

Chemopreventive Activity

Abstract Background Gastric carcinoma still remains the second most common cause of cancer mortality in the world. Chrysin, as a flavone, has showed cancer chemopreventive activity. The cellular and molecular mechanisms of chrysin in cancer cells have not been fully understood. Objective In this study, we investigate expression levels of let-7a, miR-9, mir-18a, miR-21, miR-22, miR-34a, miR-126 and mir-221 to describe the anti-cancer effects of chrysin. Materials and Methods The cytotoxic effects of chrysin were assessed using MTT assay. The effect of chrysin on the microRNAs expression was determined by qRT-PCR. Results The MTT results for different concentrations of chrysin at different times on the Gastric carcinoma cells showed that IC50 for chrysin was 68.24 µM after 24 h of treatment. Expression analysis identified that miR-18, miR-21 and miR-221 were down regulated whereas let-7a, miR-9, miR-22, miR-34a and miR-126 were up regulated in Gastric carcinoma cell line (p<0.05). Conclusion Treatment with chrysin can alter the miRNAs expression and these findings might be an explanation for molecular mechanism of chrysin effect on gastric cancer.

Download Full-text

REG I protein mediates an anti-apoptotic effect of STAT3 signaling in gastric cancer cells

Carcinogenesis ◽

10.1093/carcin/bgm250 ◽

2007 ◽

Vol 29 (1) ◽

pp. 76-83 ◽

Cited By ~ 51

Author(s):

A. Sekikawa ◽

H. Fukui ◽

S. Fujii ◽

K. Ichikawa ◽

S. Tomita ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Gastric Cancer Cells ◽

Stat3 Signaling ◽

Apoptotic Effect ◽

Reg I

Download Full-text

In vitro combination effect of 5-fluorouracil and cisplatin on the proliferation, morphology and expression of Ki-67 antigen in human gastric cancer cells

Anti-Cancer Drugs ◽

10.1097/00001813-199711000-00011 ◽

1997 ◽

Vol 8 (10) ◽

pp. 1000-1006 ◽

Cited By ~ 2

Author(s):

Toshio Imada ◽

Yasushi Rino ◽

Makoto Takahashi ◽

Tomishige Amano ◽

Osamu Kusada ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Human Gastric Cancer ◽

Combination Effect ◽

Gastric Cancer Cells ◽

Ki 67

Download Full-text

Tanshinone IIA induces ferroptosis in gastric cancer cells through p53-mediated SLC7A11 down-regulation

Bioscience Reports ◽

10.1042/bsr20201807 ◽

2020 ◽

Vol 40 (8) ◽

Cited By ~ 1

Author(s):

Zhenhua Guan ◽

Jing Chen ◽

Xueliang Li ◽

Na Dong

Keyword(s):

Gastric Cancer ◽

Lipid Peroxidation ◽

Cancer Cells ◽

Salvia Miltiorrhiza ◽

Chinese Herb ◽

Tanshinone Iia ◽

Gastric Cancer Cells ◽

P53 Expression ◽

Anti Cancer ◽

Pharmacologically Active

Abstract Gastric cancer represents a malignant type of cancer worldwide. Tanshinone IIA (Tan IIA), a pharmacologically active component isolated from the rhizome of the Chinese herb Salvia miltiorrhiza Bunge (Danshen), has been reported to possess an anti-cancer effect in gastric cancer. However, its mechanisms are still not fully understood. In the present study, we found that Tan IIA induced ferroptosis in BGC-823 and NCI-H87 gastric cancer cells. Tan IIA increased lipid peroxidation and up-regulated Ptgs2 and Chac1 expression, two markers of ferroptosis. Ferrostatin-1 (Fer-1), an inhibitor of lipid peroxidation, inhibited Tan IIA caused-lipid peroxidation and Ptgs2 and Chac1 expression. In addition, Tan IIA also up-regulated p53 expression and down-regulated xCT expression. Tan IIA caused decreased intracellular glutathione (GSH) level and cysteine level and increased intracellular reactive oxygen species (ROS) level. p53 knockdown attenuated Tan IIA-induced lipid peroxidation and ferroptosis. Tan IIA also induced lipid peroxidation and ferroptosis in BGC-823 xenograft model, and the anti-cancer effect of Tan IIA was attenuated by Fer-1 in vivo. Therefore, Tan IIA could suppress the proliferation of gastric cancer via inducing p53 upregulation-mediated ferroptosis. Our study have identified a novel mechanism of Tan IIA against gastric cancer, and might provide a critical insight into the application of Tan IIA in gastric cancer intervention.

Download Full-text

Blocking autophagy enhances the pro-apoptotic effect of bufalin on human gastric cancer cells through endoplasmic reticulum stress

Biology Open ◽

10.1242/bio.026344 ◽

2017 ◽

Vol 6 (10) ◽

pp. 1416-1422 ◽

Cited By ~ 13

Author(s):

Hongyan Zhao ◽

Qinghua Li ◽

Jie Pang ◽

Huilin Jin ◽

Hongwei Li ◽

...

Keyword(s):

Gastric Cancer ◽

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Cancer Cells ◽

Human Gastric Cancer ◽

Gastric Cancer Cells ◽

Apoptotic Effect

Download Full-text

Combinations of vitamins A, D2 and D3 have synergistic effects in gastric and colon cancer cells

Functional Foods in Health and Disease ◽

10.31989/ffhd.v9i12.646 ◽

2019 ◽

Vol 9 (12) ◽

pp. 749

Author(s):

Sheila Wicks ◽

Temitope O Lawal ◽

Nishikant Raut ◽

Shitalben Patel ◽

Gail Mahady

Keyword(s):

Gastric Cancer ◽

Colon Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Synergistic Effects ◽

Cancer Cell Lines ◽

Gastric Cancer Cells ◽

P53 Expression ◽

Colon Cancer Cell Lines

Background: Vitamin D was first hypothesized to play a role in cancer chemoprevention in 1980 when it was observed that there was a higher rate of colon cancer in the Northern USA as compared with populations living in the South. While cholecalciferol (vitamin D3) has been tested in many cancer cell lines, published results for ergocalciferol (vitamin D2) are lacking for most epithelial cell cancers, and combination studies of both D2 and D3 and vitamin A (retinoic acid) are lacking in general. The goal of the study was to investigate the effects of vitamins D2, D3, and A, and combinations on the growth of all gastric and colon cancer cell lines in vitro.Methods: Cell viability and cytotoxicity were determined using the CellTiter-Glo® 2.0, caspase and cytotoxicity activities were determined with Caspase-Glo® 3/7, Caspase 8, ApoTox-Glo™ Triplex Assay. Autophagy was determined using the CYTO-ID® Autophagy Detection Kit 2.0. Gene expression studies were performed using qPCR.Results: Both vitamin D2 and D3 inhibited the growth of all cell lines tested. The IC50 ranged from 19-56 μM. However, when combined (1:1), the IC50 for the combination of D2 and D3 was significantly reduced to a range of 5-6.0 μM indicating synergism. Vitamin A in the form of all trans-retinoic acid (ATRA) also inhibited the growth of all cell lines tested with an IC50 range of 2.6 to 5.6 μM. When ATRA was combined with D2 and D3, the IC50s were again significantly reduced to 0.65 to 1.4 μM, indicating synergistic effects. In gastric and colon cancer cell lines, the combination induced apoptosis via caspase 3/7 and 8, increased the Bax/Bcl-2 ratio; induced autophagy in SW480 cells, increased p53 expression and inhibited the expression of HDACs.Conclusion: Our data demonstrate that vitamins D2, D3 and ATRA reduce the proliferation of colon and gastric cancer cells by increasing Bax expression and the Bax/Bcl-2 ratio, and by increasing caspase activities in favor of apoptosis. The ATRA+D2+D3 combination had synergistic effects in all cell lines tested. In HCT 116 colon cancer and AGS gastric cancer cells, the combination also inhibited HDAC 1/3 and SIRT1/3 and increased p53 expression. While in SW480 colon cancer cells the combination also induced autophagy.Key words: apoptosis, autophagy cholcalciferol, ergocalciferol, gastric cancer, colon cancer, caspase, HDAC inhibitors, SIRT1, synergism

Download Full-text

The Blepharis persica seed hydroalcoholic extract synergistically enhances the apoptotic effect of doxorubicin in human colon cancer and gastric cancer cells

Molecular Biology Reports ◽

10.1007/s11033-019-04711-z ◽

2019 ◽

Vol 47 (2) ◽

pp. 843-853 ◽

Cited By ~ 2

Author(s):

Kian Aghaabbasi ◽

Nahid Askari ◽

Hassan Hassani Kumleh ◽

Masoud Torkzadeh-Mahani ◽

Abdullah Ramzani-Ghara

Keyword(s):

Gastric Cancer ◽

Colon Cancer ◽

Cancer Cells ◽

Human Colon ◽

Gastric Cancer Cells ◽

Human Colon Cancer ◽

Hydroalcoholic Extract ◽

Apoptotic Effect

Download Full-text

Enhancement of Proliferation and Invasion of Gastric Cancer Cell by KDM5C Via Decrease in p53 Expression

Technology in Cancer Research & Treatment ◽

10.1177/1533034616629261 ◽

2016 ◽

Vol 16 (2) ◽

pp. 141-149 ◽

Cited By ~ 9

Author(s):

Liming Xu ◽

Wei Wu ◽

Guilian Cheng ◽

Mingjie Qian ◽

Kewei Hu ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Messenger Rna ◽

Gastric Cancer Cell ◽

Ectopic Expression ◽

Invasive Potential ◽

Gastric Cancer Cells ◽

P53 Expression ◽

Proliferation And Invasion

Gastric cancer is a malignancy with high incidence and the second leading cause of cancer death worldwide. Development of efficient therapies against gastric cancer is urgent. Until now, the mechanisms of gastric cancer genesis remain elusive. The KDM5C is a histone demethylase that promotes cancer cell growth and is enriched in drug-resistant cancer cells. But the pathogenic breadth and mechanistic aspects of this effect relative to gastric cancer have not been defined. In present study, we found that KDM5C was overexpressed in gastric cancer cell lines and gastric cancer tissues but not in normal gastric tissues. The proliferation and invasive potential of gastric cancer cells was significantly increased by ectopic expression of KDM5C. Contrarily, RNA interference targeting KDM5C in gastric cancer cells significantly decreased the proliferation and invasive potential of cells. Moreover, we also found that the expression of p53 was modulated by KDM5C. Cells with overexpression of KDM5C exhibited greatly decreased p53 expression, whereas silencing of KDM5C expression dramatically increased p53 expression at both the messenger RNA and protein levels. Inhibition of p53 by small-interfering RNA reversed the shKDM5C-induced proliferation and invasion. Our results collectively suggested that KDM5C played a role in gastric cancer cells proliferation and invasion, which may be partly associated with the p53 expression.

Download Full-text